This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The model of HIV sexual transmission in the male genital tract has not been well developed and this has hindered our understanding of how male circumcision prevents against HIV infection. We aimed to create a more comprehensive model of HIV transmission in men using the rhesus macaque model of penile transmission and circumcision. We have circumcised four macaques and are following changes in penile skin thickness, target cells, and moisture absorbing capabilities of the penile shaft after circumcision to determine why circumcision protects against transmission. We are also using photoactivatable GFP-Vpr HIVBal in culture to determine how the virus penetrates the penile eithelium. The genital tracts of uncircumcised male rhesus macaques (Macaca mulatta) Tulane National Primate Research Centers were inoculated with photoactivatable GFP-Vpr HIV[unreadable][unreadable]Bal in vivo, and penile tissue was removed during necropsy. Tissue cryosections were stained for Langerhans cells, CD4+ T-cells, keratin, and intercellular junctions. Images were obtained with DeltaVision RT systems and analyzed with SoftWorx software. Four uncircumcised male macaques were separately circumcised at Tulane. Trans-epithelial water loss and skin capacitance of the macaque penis before and after circumcision were non-invasively measured using the Vapometer and MoistureMeter. HIV particles were predominantly visualized in the keratin of penile epithelia, which tends to be thinner in the circumcised penis. 3-8% of virions were seen in deeper epithelial strata, with penetrating virions seen at depths of up to 60 microns from the surface and occasionally near target cells. These results were similar to identical of those performed by Dr. Minh in Chicago, thus validating the use of the rhesus explant model. These findings represent potential routes of HIV transmission in the male genital tract. Building a clearer model of transmission will aid in the development of future HIV prevention methods.